Gene Discovery- Immunotherapy has been most successful when targeted to differentiation antigens expressed on hematopoietic tumors and melanomas in large part because the target antigens are not expressed on essential cells or organs. Other cancers in which this approach could be successful are prostate, breast and ovary. To identify target antigens in prostate and breast cancers we have developed a computer based method to search the EST data base for ESTs that are expressed in prostate or breast cancer and not in other essential organs or cells. We have validated this approach experimentally and used it to identify several genes/proteins expressed in prostate cancer and not in essential normal organs. These include TARP, PAGE4, and GDEP. TARP is a mitochondrial protein that is also expressed in breast cancer. PAGE4 is a cytoplasmic protein. In the past year we have identified a new gene NGEP expressed in prostate and prostate cancer, encoding a membrane protein with seven membrane-spanning domains. We also identified POTE, a large gene family, expressed in prostate, ovary, testis, placenta and many cancers. We are preparing polyclonal and monoclonal antibodies to both these proteins.